This research proposes the continuation of a thorough microrheological study of the flow patterns and distributions of fluid velocity and shear rate in various regions of disturbed flow in the human cardio- and cerebrovascular systems. This will be achieved through direct observation and filming of the behavior of blood cells and model particles flowing in isolated transparent natural bessels prepared from humans postmortem by the method developed by the applicant. Specifics aims of the proposed research are: (1) to obtain precise and detailed flow patterns in regions of disturbed flow in the human circulation under normal (physiological) and altered (pathological) flow conditions; (2) to acquire information on the distributions of fluid velocity and shear rate existing in the regions of disturbed flow in order to identify the regions of high and low shear; and (3) to correlate the results with the incidence of vascular disease in vivo. Long term objectives of the proposed research are: (1) to arrive at a better understanding of fluid dynamics of the human circulation under normal and altered flow conditions; and (2) to clarify the possible connection between flow and the localization of thrombosis, atherosclerosis and aneurysm formation. Plans for the next three years are to continue the present fluid mechanical studies of the human coronary and cerebral arterial circulations. To clarify the uncertainty surrounding the origin of flow disturbances observed in coronary arteries from aged subjects, i.e. whether they were secondary phenomena following the anatomical and morphological change in vessel geometry and wall structure due to aging and the formation of atherosclerotic plaques and wall thickenings, we will first focus our flow studies on young vessels. Then, we will proceed to flow studies in aged coronary arteries with severe atherosclerotic lesions to find the relationship between the locations of advanced and calcified plaque and those of the incipient atherosclerotic lesions which were found in younger subjects. In the cerebral circulation, we will focus our study on the pathogenesis of saccular aneurysms at the major bifurcations and T-junctions of the circle of Willis. We will also improve our electric circuit model of the human circle of Willis and study the effects of multi vessel occlusion (including cases of congenital defects and malformation of vessels) on redistribution of the flow through the arterial network.